Brave New Worlds

In the United States, babies just minutes old are stabbed in the heel with a lancet. The blood obtained is used to screen for phenylketonuria, congenital hypothyroidism, cystic fibrosis and an inability to fully metabolize galactose—conditions that, if undiagnosed, can lead to significant medical problems. Today's tests rely on biochemical markers. But a decade from now, we will be able to extract far more information from that heel prick, using the child's DNA. By then we will have deciphered the genetic component of hundreds, perhaps thousands, of diseases, and a single drop of blood will yield enough DNA to test for them all.

But what kind of knowledge will we gain? Medicine, up to now, has centered on the retrospective analysis of symptoms to uncover underlying causes. We expect our physicians to tell us with certainty, "You have diabetes," "You have a kidney stone." But a glimpse into the newborn's genome will give us diagnostic information that is more complex and less definitive—information about increased risk and predisposition. The certainty we expect from medical tests will be replaced by a foreshadowing of dangers far in the future, many of which we can do little about.

In Building Genetic Medicine, Shobita Parthasarathy explores how this new world has begun to play out. She describes the history and politics of genetic testing for increased susceptibility to breast and ovarian cancer in the United Kingdom and the United States, suggesting that their radically different perspectives on health care have led to radically different responses to the advent of such testing. Her rigorous analysis identifies a characteristic national toolkit on each side of the Atlantic—an intertwined set of cultural beliefs, practices and traditions—that circumscribes the ways in which innovation is incorporated into the ongoing practice of medicine. Each national toolkit gives rise in turn to a unique architecture of genetic testing, which defines how patients, physicians, testing centers and payers relate to one another, and which determines how the test reshapes notions of risk and treatment. By analyzing how testing for the BRCA1 and BRCA2 genes is integrated into British and American medicine, Parthasarathy provides a unique case study in the social construction of illness and cure in contemporary Western societies.

At first glance, the sequencing of the nucleotides in our genome would seem the very model of how to find objective, context-independent truth. But the book is at its best when exposing the fallacy that genetic information is unambiguous. The rub, of course, is not in the sequence information—genetic technologies have become fast, accurate and reliable. Rather, ambiguity resides in the interpretation of the results. Only about 1 in 10 cases of breast cancer can be traced to mutations in the BRCA1 or BRCA2 genes. Furthermore, the BRCA1 and BRCA2 genes vary in the human population (as do all genes), and not all of the mutations result in an increased risk of breast or ovarian cancer. Finally, women who test positive for one of the mutations that are associated with increased risk face a set of difficult choices: Should they initiate preventive drug therapy, with its attendant risks? Undergo prophylactic mastectomy? Have their ovaries removed? Under these circumstances, argues Parthasarathy, the incorporation of genetic testing for breast cancer into medical practice has been far from straightforward.

In the United States, where the allocation of medical resources, including genetic testing, is determined primarily in the private sector by health maintenance organizations and insurance companies, access to medical care is tethered to notions of individual choice. In this setting, BRCA testing has been heralded as a vehicle for empowering women by giving them access to crucial information about their bodies. The sole provider of BRCA testing in the United States, Myriad Genetics, has recently begun advertising its services directly to American women, casting the test as one more way for women to shape their own care. Physicians are still part of the process—they must sign the test-request forms and order the blood samples. But one wonders: Are we just a step away from American physicians being relieved of their traditional responsibility as brokers and providers of complex medical information? Demand for the test is driven not by potential benefits to the patient as determined by her physician or by the optimal social allocation of health care dollars, but by the patient's expectations and means. A press release from Myriad Genetics boasts that 62 percent of the women they surveyed said that if necessary they would switch physicians to gain access to the test.

The British health-care system's response to BRCA testing stands in sharp contrast to this situation. Parthasarathy offers a brief and enlightening history of the National Health Service (NHS), the publicly funded organization that has been the principal provider of health care services in the United Kingdom since World War II. Under the NHS, concepts wholly foreign to American health care, such as equal access and triage, have shaped views of the BRCA test's usefulness. Genetic testing for a predisposition to breast cancer is not construed as technology to which every patient is entitled, but instead as one more weapon in the arsenal of treatment and prevention—a tool to be used only for patients with an extensive family history of breast or ovarian cancer. The NHS, and by extension the British citizenry, have from the outset accepted a triage model: Physicians and oversight boards determine the allocation of finite health care resources. In this setting, BRCA testing is available only to women who meet a series of established national criteria that place them in the high-risk category.

Building Genetic Medicine would be well worth reading if it did nothing more than carefully lay out how differences between the British and American health care systems have affected BRCA testing. But this is an ambitious book, which also analyzes the impact of BRCA testing on the various stakeholders in the breast cancer wars. The availability of a test that provides information about disease risk, decades before the disease is expected to show up, has rattled everyone's cage.

Patient advocates in the United States, for instance, worry about the impact of BRCA testing on patient access to insurance and employment. (This concern, incidentally, leads many patients to pay for the testing themselves to keep the results out of their insurance files.) In contrast, in the United Kingdom, where access to health care is guaranteed, instead of worry about discrimination there is concern about the allocation of resources to genetic testing rather than to cancer prevention.

Physicians, too, play very different roles in the two countries. Myriad Genetics sees U.S. physicians as gate-openers, driven by patient requests to increase access to BRCA testing. Physicians in the United Kingdom, in contrast, play a gate-keeper role, restricting BRCA testing to those whose medical and family histories indicate that the cost is warranted.

Also, differences between the two health care systems result in the test being defined differently in the two settings. In the United States, the BRCA test is a profitable commodity competing for the attention (and dollars) of consumers accustomed to choice. Building Genetic Medicine follows the efforts of Myriad Genetics as it seeks to eliminate its competition in the United States. As Parthasarathy makes clear, Myriad is playing its expected role in a system built around privatized health care. In the jostling U.S. market, Myriad defines itself as a company that provides cutting-edge testing services to any consumer who wants to know her BRCA status. Furthermore, the patent on BRCA testing is Myriad's main asset. As a publicly traded company, it must both protect that asset against infringement and expand the market for the test.

When Myriad Genetics sought to protect its patent on BRCA testing in the United Kingdom, however, the culture of entrepreneurship collided head-on with the concept of universal health care. The British health care establishment, patient-rights groups and policy makers responded vigorously, questioning the company's patent claims. The argument that blood samples should be sent from the United Kingdom to Salt Lake City for analysis was derided. Myriad's request that the NHS pay royalties to the company for every BRCA test conducted was seen as another example of American greed at work. In the end, the company abandoned its efforts to control BRCA testing in the United Kingdom, bowing to the architecture it had come up against.

This century began with the completion of the sequencing of the human genome, which ushered in a new era in medicine. For the first time, the possibility of uncovering the genetic contributions to virtually all illnesses seems within reach. Not only are we discovering the damaged genes responsible for simple inherited conditions, we are learning to identify the suites of interacting genes that contribute to more-complex medical problems. And it has become apparent that the identification of any disease-related gene or set of genes will soon be followed by a commercial genetic test.

Is this progress? On one level, the answer is clear: The uncovering of genetic underpinnings has led to deep insights regarding the mechanisms of disease. Ideally, such insights will point the way to new methods of screening, alleviation, cure and prevention. Medicine may be undergoing a profound transformation as it moves from symptom-based to cause-based diagnosis. But like all scientific transformations, the genetic revolution is deeply embedded in a social context. The ability to know our genome from birth simultaneously holds out the promise of succor and the prospect of unalterable stigmatization; the road we follow will be determined by the way societies incorporate this new knowledge. Building Genetic Medicine is an enlightening overview of one of the first skirmishes of our genetic century. The book echoes the battle cry of the feminist revolution; here, the genetic is political.